Ignite Creation Date:
2024-05-06 @ 1:11 PM
Last Modification Date:
2024-10-26 @ 1:10 PM
Study NCT ID:
NCT03959085
Status:
RECRUITING
Last Update Posted:
2024-04-22
First Post:
2019-05-20
Brief Title:
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL Mixed Phenotype Acute Leukemia and B-LLy
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
A Phase 3 Randomized Trial of Inotuzumab Ozogamicin NSC 772518 for Newly Diagnosed High-Risk B-ALL Risk-Adapted Post-Induction Therapy for High-Risk B-ALL Mixed Phenotype Acute Leukemia and Disseminated B-LLy
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase III trial studies whether inotuzumab ozogamicin added to post-induction chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia B-ALL improves outcomes This trial also studies the outcomes of patients with mixed phenotype acute leukemia MPAL and B-lymphoblastic lymphoma B-LLy when treated with ALL therapy without inotuzumab ozogamicin Inotuzumab ozogamicin is a monoclonal antibody called inotuzumab linked to a type of chemotherapy called calicheamicin Inotuzumab attaches to cancer cells in a targeted way and delivers calicheamicin to kill them Other drugs used in the chemotherapy regimen such as cyclophosphamide cytarabine dexamethasone doxorubicin daunorubicin methotrexate leucovorin mercaptopurine prednisone thioguanine vincristine and pegaspargase or calaspargase pegol work in different ways to stop the growth of cancer cells either by killing the cells by stopping them from dividing or by stopping them from spreading This trial will also study the outcomes of patients with mixed phenotype acute leukemia MPAL and disseminated B lymphoblastic lymphoma B-LLy when treated with high-risk ALL chemotherapy
The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic Leukemia HR B-ALL The first part of the study includes the first two phases of therapy Induction and Consolidation This part will collect information on the leukemia as well as the effects of the initial treatment to classify patients into post-consolidation treatment groups On the second part of this study patients with HR B-ALL will receive the remainder of the chemotherapy cycles interim maintenance I delayed intensification interim maintenance II maintenance with some patients randomized to receive inotuzumab The patients that receive inotuzumab will not receive part of delayed intensification Other aims of this study include investigating whether treating both males and females with the same duration of chemotherapy maintains outcomes for males who have previously been treated for an additional year compared to girls as well as to evaluate the best ways to help patients adhere to oral chemotherapy regimens Finally this study will be the first to track the outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia B-LLy or Mixed Phenotype Acute Leukemia MPAL when treated with B-ALL chemotherapy
The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic Leukemia HR B-ALL The first part of the study includes the first two phases of therapy Induction and Consolidation This part will collect information on the leukemia as well as the effects of the initial treatment to classify patients into post-consolidation treatment groups On the second part of this study patients with HR B-ALL will receive the remainder of the chemotherapy cycles interim maintenance I delayed intensification interim maintenance II maintenance with some patients randomized to receive inotuzumab The patients that receive inotuzumab will not receive part of delayed intensification Other aims of this study include investigating whether treating both males and females with the same duration of chemotherapy maintains outcomes for males who have previously been treated for an additional year compared to girls as well as to evaluate the best ways to help patients adhere to oral chemotherapy regimens Finally this study will be the first to track the outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia B-LLy or Mixed Phenotype Acute Leukemia MPAL when treated with B-ALL chemotherapy
Detailed Description:
PRIMARY OBJECTIVE
I To compare in a randomized manner the 5-year disease-free survival DFS for children and young adults with High Risk HR B-cell acute lymphoblastic leukemia B-ALL treated with modified Berlin-Frankfurt-Munster mBFM chemotherapy without delayed intensification DI part 2 but with the addition of two blocks of inotuzumab ozogamicin versus those treated with full mBFM chemotherapy backbone including DI Part 2 without the addition of inotuzumab ozogamicin
SECONDARY OBJECTIVES
I To describe the 5-year DFS for a favorable risk subset of National Cancer Institute NCI HR B-ALL HR-Fav when treated with mBFM chemotherapy with a single high-dose methotrexate HD-MTX interim maintenance IM phase and treatment duration of 2 years from the start of IM regardless of sex
II To determine the toxicity and tolerability of inotuzumab ozogamicin integrated into the mBFM chemotherapy backbone in HR B-ALL including toxicity experienced during phases of therapy subsequent to inotuzumab ozogamicin
III To describe the 5-year event-free survival EFS for patients with mixed phenotype acute leukemia MPAL receiving mBFM HR B-ALL therapy that includes a second IM phase with Capizzi intravenous IV methotrexate without leucovorin rescue plus pegaspargase or calaspargase pegol C-MTX
IV To describe the 5-year EFS for patients with disseminated Murphy stage III-IV B-cell lymphoblastic lymphoma B-LLy receiving mBFM HR B-ALL therapy that includes a second IM phase with C-MTX
EXPLORATORY OBJECTIVES
I To describe the therapy administered disease response and survival outcomes of patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy either during Induction at end of induction EOI or at end of consolidation EOC
II To define the prevalence and significance of minimal marrow disease MMD at diagnosis and bone marrow minimal residual disease MRD at EOI in disseminated B-LLy
III To determine the impact of proposed adherence-enhancing interventions on adherence to oral 6-mercaptopurine in patients with ALL
OUTLINE All patients receive the same Induction and Consolidation chemotherapy Patients with HR-Fav B-ALL are assigned to Arm I Patients with HR B-ALL are randomized to Arm II or III Patients with MPAL are assigned to Arm IV and patients with B-LLy are assigned to Arm V
All patients with B-ALL receive Induction and Consolidation therapy
INDUCTION Patients receive cytarabine intrathecally IT on day 1 and central nervous system CNS2 patients also receive cytarabine IT on days 4 5 or 6 and 11 or 12 Patients also receive vincristine intravenously IV on days 1 8 15 and 22 daunorubicin IV over 1-15 minutes days 1 8 15 and 22 pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase intramuscularly IM on day 4 and methotrexate IT on days 8 and 29 and on days 15 and 22 for CNS3 patients Patients 10 years old receive dexamethasone orally PO twice daily BID or IV on days 1-14 patients 10 years old receive prednisolone PO BID or IV on days 1-28 Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
CONSOLIDATION Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29 cytarabine IV over 1-30 minutes or subcutaneously SC on days 1-4 8-11 29-32 and 36-39 mercaptopurine PO once daily QD on days 1-14 and 29-42 and methotrexate IT on days 1 8 15 and 22 CNS3 patients receive methotrexate IT on days 1 and 8 Patients also receive vincristine IV on days 15 22 43 and 50 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on days 15 and 43 Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity Additionally patients with testicular disease at diagnosis that does not resolve by the end of induction will undergo radiation therapy over 12 once daily fractions Calaspargase pegol can only be given to patients less than 22 years of age
POST-CONSOLIDATION THERAPY After Consolidation based on clinical features and response patients with B-ALL are designated as HR-Fav or HR B-ALL Patients with HR-Fav B-ALL are assigned to Arm I Patients with HR B-ALL are randomized to Arm II or III Patients with MPAL and B-LLy are assigned to therapy arms Arms IV and V that are identical to Arm II Patients that are 10 years have CNS1 no testicular leukemia with favorable cytogenetics ETV6 RUNX1 fusion or double trisomies 4 and 10 24 hours of steroids in the two weeks prior to diagnosis and EOI MRD 001 are assigned to Arm I Patients with HR B-ALL who are surface CD22 positive at diagnosis and have MRD 001 by the end of Consolidation are randomized to either Arm II or III
ARM I HR-FAV B-ALL Patients that are 10 years have CNS1 status no testicular leukemia with favorable cytogenetics ETV6 RUNX1 fusion or double trisomies 4 and 10 24 hours of steroids in the two weeks prior to diagnosis and EOI MRD 001
INTERIM MAINTENANCE Patients receive vincristine IV on days 1 15 29 and 43 high dose methotrexate IV over 24 hours on days 1 15 29 and 43 leucovorin PO or IV on days 3-4 17-18 31-32 and 45-46 mercaptopurine PO QD on days 1-14 15-28 29-42 and 43-56 and methotrexate IT on days 1 and 29 Treatment continues for 9 weeks in the absence of disease progression or unacceptable toxicity
DELAYED INTENSIFICATION PART I Patients receive methotrexate IT on day 1 dexamethasone PO BID or IV on days 1-7 and 15-21 vincristine IV on days 1 8 and 15 doxorubicin IV over 1-15 minutes or up to 1 hour on days 1 8 and 15 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4 Treatment Parts I and II of Delayed Intensification continues for 9 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
DELAYED INTENSIFICATION PART II Patients receive cyclophosphamide IV over 30-60 minutes on day 29 thioguanine PO on days 29-42 cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39 methotrexate IT on days 29 and 36 vincristine IV on days 43 and 50 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 43 Treatment Parts I and II of Delayed Intensification continues for 9 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
MAINTENANCE Patients receive methotrexate IT on days 1 and 29 for cycles 1-4 and day 1 for subsequent cycles Patients also receive vincristine IV on day 1 prednisolone PO BID or IV on days 1-5 mercaptopurine PO QD on days 1-84 and methotrexate PO on days 8 15 22 29 excluded in cycles 1-4 36 43 50 57 64 71 and 78 Cycles repeat every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity
Patients with HR B-ALL who have MRD 001 by the end of Consolidation and leukemic blasts positive for surface CD22 at diagnosis are randomized to Arm II or Arm III
ARM II HR B-ALL CONTROL INTERIM MAINTENANCE I Patients receive vincristine IV on days 1 15 29 and 43 high dose methotrexate IV over 24 hours on days 1 15 29 and 43 leucovorin PO or IV on days 3-4 17-18 31-32 45-46 mercaptopurine PO QD on days 1-14 15-28 29-42 and 43-56 and methotrexate IT on days 1 and 29 Treatment continues for 9 weeks in the absence of disease progression or unacceptable toxicity
DELAYED INTENSIFICATION PART I Patients receive methotrexate IT on day 1 dexamethasone PO BID or IV on days 1-7 and 15-21 vincristine IV on days 1 8 and 15 doxorubicin IV over 1-15 minutes or up to 1 hour on days 1 8 and 15 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4 Treatment Parts I and II of Delayed Intensification continues for 9 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
DELAYED INTENSIFICATION PART II Patients receive cyclophosphamide IV over 30-60 minutes on day 29 thioguanine PO on days 29-42 cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39 methotrexate IT on days 29 and 36 vincristine IV on days 43 and 50 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 43 Treatment Parts I and II of Delayed Intensification continues for 9 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
INTERIM MAINTENANCE II Patients receive vincristine on days 1 11 21 31 and 41 methotrexate IV over 2-15 minutes or 10-15 minutes on days 1 11 21 31 and 41 methotrexate IT on days 1 and 31 and pegaspargase or calaspargase pegol IV over 1-2 hours on days 2 and 22 pegaspargase or 23 calaspargase or pegaspargase IM on days 2 and 22 Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
ARM III HR B-ALL EXPERIMENTAL INOTUZUMAB OZOGAMICIN InO BLOCK 1 Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1 8 and 15 and methotrexate IT on day 1 Treatment continues for 4 weeks in the absence of disease progression or unacceptable toxicity
INTERIM MAINTENANCE I Patients receive vincristine IV on days 1 15 29 and 43 high dose methotrexate IV over 24 hours on days 1 15 29 and 43 leucovorin PO or IV on days 3-4 17-18 31-32 and 45-46 mercaptopurine PO on days 1-14 15-28 29-42 and 43-56 and methotrexate IT on days 1 and 29 Treatment continues for 9 weeks in the absence of disease progression or unacceptable toxicity
DELAYED INTENSIFICATION Part I Patients receive methotrexate IT on day 1 dexamethasone PO BID or IV on days 1-7 and 15-21 vincristine IV on days 1 8 and 15 doxorubicin IV over 1-15 minutes or up to 1 hour on days 1 8 and 15 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4 Treatment Parts I and II of Delayed Intensification continues for 5 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
InO BLOCK 2 Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1 8 and 15 Treatment continues for 4 weeks in the absence of disease progression or unacceptable toxicity
INTERIM MAINTENANCE II Patients receive vincristine IV on days 1 11 21 31 and 41 methotrexate IV on days 1 11 21 31 and 41 methotrexate IT on days 1 and 31 and pegaspargase or calaspargase pegol IV over 1-2 hours on days 2 and 22 pegaspargase or 23 calaspargase or pegaspargase IM on days 2 and 22 Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
ARMS II AND III HR B-ALL MAINTENANCE Patients receive vincristine IV on day 1 prednisolone PO BID or IV on days 1-5 mercaptopurine PO on days 1-84 methotrexate PO on days 8 15 22 29 excluded in cycles 1 and 2 36 43 50 57 64 71 and 78 and methotrexate IT on days 1 and 29 of cycles 1-2 for patients who do not receive cranial radiation Cycles repeat every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity Patients with CNS3 disease undergo cranial radiation therapy over 10 fractions during the first 4 weeks
ARM IV MPAL INDUCTION Patients receive cytarabine IT on day 1 and CNS2 patients also receive cytarabine IT on days 4 5 or 6 and 11 or 12 Patients also receive vincristine IV on days 1 8 15 and 22 daunorubicin IV over 1-15 minutes days 1 8 15 and 22 pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4 and methotrexate IT on days 8 and 29 and on days 15 and 22 for CNS3 patients Patients 10 years old receive dexamethasone PO BID or IV on days 1-14 patients 10 years old receive prednisolone PO BID or IV on days 1-28 Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
CONSOLIDATION Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29 cytarabine IV over 1-30 minutes or SC on days 1-4 8-11 29-32 and 36-39 mercaptopurine PO on days 1-14 and 29-42 methotrexate IT on days 1 8 15 and 22 excluded on days 15 and 22 for CNS3 patients vincristine IV on days 15 22 43 and 50 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on days 15 and 43 Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity Patients with testicular disease at diagnosis that does not resolve by the end of induction will and continued evidence of testicular disease at end of induction undergo testicular radiation over 12 once-daily fractions Calaspargase pegol can only be given to patients less than 22 years of age
ARM V B-LLY INDUCTION Patients receive cytarabine IT on day 1 and CNS2 patients also receive cytarabine IT on days 4 5 or 6 and 11 or 12 Patients also receive vincristine IV on days 1 8 15 and 22 daunorubicin IV over 1-15 minutes days 1 8 15 and 22 pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4 and methotrexate IT on days 8 and 29 and on days 15 and 22 for CNS3 patients Patients 10 years old receive dexamethasone PO BID or IV on days 1-14 patients 10 years old receive prednisolone PO BID or IV on days 1-28 Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
CONSOLIDATION Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29 cytarabine IV over 1-30 minutes or SC on days 1-4 8-11 29-32 and 36-39 mercaptopurine PO on days 1-14 and 29-42 methotrexate IT on days 1 8 15 and 22 excluded on days 15 and 22 CNS3 patients vincristine IV on days 15 22 43 and 50 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on days 15 and 43 Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity Patients with testicular disease at diagnosis that does not resolve by the end of induction will and continued evidence of testicular disease at end of induction undergo testicular radiation therapy over 12 once-daily fractions Calaspargase pegol can only be given to patients less than 22 years of age
ARM IV AND V MPAL AND B-LLY Post-Consolidation Therapy INTERIM MAINTENANCE I Patients receive vincristine IV on days 1 15 29 and 43 high dose methotrexate IV over 24 hours on days 1 15 29 and 43 leucovorin PO or IV on days 3-4 17-18 31-32 and 45-46 methotrexate IT on days 1 and 29 and mercaptopurine PO QD on days 1-14 15-28 29-42 and 43-56 Treatment continues for 9 weeks in the absence of disease progression or unacceptable toxicity
DELAYED INTENSIFICATION PART I Patients receive methotrexate IT on day 1 dexamethasone PO BID or IV on days 1-7 and 15-21 vincristine IV on days 1 8 and 15 doxorubicin IV over 1-15 minutes or up to 1 hour on days 1 8 and 15 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4 Treatment Parts I and II of Delayed Intensification continues for 9 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
DELAYED INTENSIFICATION PART II Patients receive cyclophosphamide IV over 30-60 minutes on day 29 thioguanine PO on days 29-42 cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39 methotrexate IT on days 29 and 36 vincristine IV or IV push over 1 minute on days 43 and 50 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 43 Treatment Parts I and II of Delayed Intensification continues for 9 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
INTERIM MAINTENANCE II Patients receive vincristine IV on days 1 11 21 31 and 41 methotrexate IV or infusion over 2-15 minutes or 10-15 minutes on days 1 11 21 31 and 41 methotrexate IT on days 1 and 31 and pegaspargase or calaspargase pegol IV over 1-2 hours on days 2 and 22 pegaspargase or calaspargase 23 or pegaspargase IM on days 2 and 22 Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
MAINTENANCE Patients receive vincristine IV on days 1 prednisolone PO BID or IV on days 1-5 mercaptopurine PO on days 1-84 methotrexate PO on days 8 15 22 29 excluded in cycles 1 and 2 36 43 50 57 64 71 and 78 and methotrexate IT on days 1 and 29 of cycles 1-2 for patients who do not receive cranial radiation Cycles repeat every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity Patients with CNS3 disease at diagnosis undergo cranial radiation therapy for 10 fractions over 4 weeks
Patients undergo blood sample collection and bone marrow aspiration and biopsy on study B-LLy patients undergo computed tomography CT magnetic resonance imaging MRI positron emission tomography PET andor bone scan on study
After completion of study treatment patients are followed up at 4 weeks then every 3 months for 2 years every 4-6 months for the third year then every 6-12 months for years 4-5
I To compare in a randomized manner the 5-year disease-free survival DFS for children and young adults with High Risk HR B-cell acute lymphoblastic leukemia B-ALL treated with modified Berlin-Frankfurt-Munster mBFM chemotherapy without delayed intensification DI part 2 but with the addition of two blocks of inotuzumab ozogamicin versus those treated with full mBFM chemotherapy backbone including DI Part 2 without the addition of inotuzumab ozogamicin
SECONDARY OBJECTIVES
I To describe the 5-year DFS for a favorable risk subset of National Cancer Institute NCI HR B-ALL HR-Fav when treated with mBFM chemotherapy with a single high-dose methotrexate HD-MTX interim maintenance IM phase and treatment duration of 2 years from the start of IM regardless of sex
II To determine the toxicity and tolerability of inotuzumab ozogamicin integrated into the mBFM chemotherapy backbone in HR B-ALL including toxicity experienced during phases of therapy subsequent to inotuzumab ozogamicin
III To describe the 5-year event-free survival EFS for patients with mixed phenotype acute leukemia MPAL receiving mBFM HR B-ALL therapy that includes a second IM phase with Capizzi intravenous IV methotrexate without leucovorin rescue plus pegaspargase or calaspargase pegol C-MTX
IV To describe the 5-year EFS for patients with disseminated Murphy stage III-IV B-cell lymphoblastic lymphoma B-LLy receiving mBFM HR B-ALL therapy that includes a second IM phase with C-MTX
EXPLORATORY OBJECTIVES
I To describe the therapy administered disease response and survival outcomes of patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy either during Induction at end of induction EOI or at end of consolidation EOC
II To define the prevalence and significance of minimal marrow disease MMD at diagnosis and bone marrow minimal residual disease MRD at EOI in disseminated B-LLy
III To determine the impact of proposed adherence-enhancing interventions on adherence to oral 6-mercaptopurine in patients with ALL
OUTLINE All patients receive the same Induction and Consolidation chemotherapy Patients with HR-Fav B-ALL are assigned to Arm I Patients with HR B-ALL are randomized to Arm II or III Patients with MPAL are assigned to Arm IV and patients with B-LLy are assigned to Arm V
All patients with B-ALL receive Induction and Consolidation therapy
INDUCTION Patients receive cytarabine intrathecally IT on day 1 and central nervous system CNS2 patients also receive cytarabine IT on days 4 5 or 6 and 11 or 12 Patients also receive vincristine intravenously IV on days 1 8 15 and 22 daunorubicin IV over 1-15 minutes days 1 8 15 and 22 pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase intramuscularly IM on day 4 and methotrexate IT on days 8 and 29 and on days 15 and 22 for CNS3 patients Patients 10 years old receive dexamethasone orally PO twice daily BID or IV on days 1-14 patients 10 years old receive prednisolone PO BID or IV on days 1-28 Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
CONSOLIDATION Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29 cytarabine IV over 1-30 minutes or subcutaneously SC on days 1-4 8-11 29-32 and 36-39 mercaptopurine PO once daily QD on days 1-14 and 29-42 and methotrexate IT on days 1 8 15 and 22 CNS3 patients receive methotrexate IT on days 1 and 8 Patients also receive vincristine IV on days 15 22 43 and 50 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on days 15 and 43 Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity Additionally patients with testicular disease at diagnosis that does not resolve by the end of induction will undergo radiation therapy over 12 once daily fractions Calaspargase pegol can only be given to patients less than 22 years of age
POST-CONSOLIDATION THERAPY After Consolidation based on clinical features and response patients with B-ALL are designated as HR-Fav or HR B-ALL Patients with HR-Fav B-ALL are assigned to Arm I Patients with HR B-ALL are randomized to Arm II or III Patients with MPAL and B-LLy are assigned to therapy arms Arms IV and V that are identical to Arm II Patients that are 10 years have CNS1 no testicular leukemia with favorable cytogenetics ETV6 RUNX1 fusion or double trisomies 4 and 10 24 hours of steroids in the two weeks prior to diagnosis and EOI MRD 001 are assigned to Arm I Patients with HR B-ALL who are surface CD22 positive at diagnosis and have MRD 001 by the end of Consolidation are randomized to either Arm II or III
ARM I HR-FAV B-ALL Patients that are 10 years have CNS1 status no testicular leukemia with favorable cytogenetics ETV6 RUNX1 fusion or double trisomies 4 and 10 24 hours of steroids in the two weeks prior to diagnosis and EOI MRD 001
INTERIM MAINTENANCE Patients receive vincristine IV on days 1 15 29 and 43 high dose methotrexate IV over 24 hours on days 1 15 29 and 43 leucovorin PO or IV on days 3-4 17-18 31-32 and 45-46 mercaptopurine PO QD on days 1-14 15-28 29-42 and 43-56 and methotrexate IT on days 1 and 29 Treatment continues for 9 weeks in the absence of disease progression or unacceptable toxicity
DELAYED INTENSIFICATION PART I Patients receive methotrexate IT on day 1 dexamethasone PO BID or IV on days 1-7 and 15-21 vincristine IV on days 1 8 and 15 doxorubicin IV over 1-15 minutes or up to 1 hour on days 1 8 and 15 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4 Treatment Parts I and II of Delayed Intensification continues for 9 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
DELAYED INTENSIFICATION PART II Patients receive cyclophosphamide IV over 30-60 minutes on day 29 thioguanine PO on days 29-42 cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39 methotrexate IT on days 29 and 36 vincristine IV on days 43 and 50 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 43 Treatment Parts I and II of Delayed Intensification continues for 9 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
MAINTENANCE Patients receive methotrexate IT on days 1 and 29 for cycles 1-4 and day 1 for subsequent cycles Patients also receive vincristine IV on day 1 prednisolone PO BID or IV on days 1-5 mercaptopurine PO QD on days 1-84 and methotrexate PO on days 8 15 22 29 excluded in cycles 1-4 36 43 50 57 64 71 and 78 Cycles repeat every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity
Patients with HR B-ALL who have MRD 001 by the end of Consolidation and leukemic blasts positive for surface CD22 at diagnosis are randomized to Arm II or Arm III
ARM II HR B-ALL CONTROL INTERIM MAINTENANCE I Patients receive vincristine IV on days 1 15 29 and 43 high dose methotrexate IV over 24 hours on days 1 15 29 and 43 leucovorin PO or IV on days 3-4 17-18 31-32 45-46 mercaptopurine PO QD on days 1-14 15-28 29-42 and 43-56 and methotrexate IT on days 1 and 29 Treatment continues for 9 weeks in the absence of disease progression or unacceptable toxicity
DELAYED INTENSIFICATION PART I Patients receive methotrexate IT on day 1 dexamethasone PO BID or IV on days 1-7 and 15-21 vincristine IV on days 1 8 and 15 doxorubicin IV over 1-15 minutes or up to 1 hour on days 1 8 and 15 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4 Treatment Parts I and II of Delayed Intensification continues for 9 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
DELAYED INTENSIFICATION PART II Patients receive cyclophosphamide IV over 30-60 minutes on day 29 thioguanine PO on days 29-42 cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39 methotrexate IT on days 29 and 36 vincristine IV on days 43 and 50 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 43 Treatment Parts I and II of Delayed Intensification continues for 9 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
INTERIM MAINTENANCE II Patients receive vincristine on days 1 11 21 31 and 41 methotrexate IV over 2-15 minutes or 10-15 minutes on days 1 11 21 31 and 41 methotrexate IT on days 1 and 31 and pegaspargase or calaspargase pegol IV over 1-2 hours on days 2 and 22 pegaspargase or 23 calaspargase or pegaspargase IM on days 2 and 22 Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
ARM III HR B-ALL EXPERIMENTAL INOTUZUMAB OZOGAMICIN InO BLOCK 1 Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1 8 and 15 and methotrexate IT on day 1 Treatment continues for 4 weeks in the absence of disease progression or unacceptable toxicity
INTERIM MAINTENANCE I Patients receive vincristine IV on days 1 15 29 and 43 high dose methotrexate IV over 24 hours on days 1 15 29 and 43 leucovorin PO or IV on days 3-4 17-18 31-32 and 45-46 mercaptopurine PO on days 1-14 15-28 29-42 and 43-56 and methotrexate IT on days 1 and 29 Treatment continues for 9 weeks in the absence of disease progression or unacceptable toxicity
DELAYED INTENSIFICATION Part I Patients receive methotrexate IT on day 1 dexamethasone PO BID or IV on days 1-7 and 15-21 vincristine IV on days 1 8 and 15 doxorubicin IV over 1-15 minutes or up to 1 hour on days 1 8 and 15 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4 Treatment Parts I and II of Delayed Intensification continues for 5 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
InO BLOCK 2 Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1 8 and 15 Treatment continues for 4 weeks in the absence of disease progression or unacceptable toxicity
INTERIM MAINTENANCE II Patients receive vincristine IV on days 1 11 21 31 and 41 methotrexate IV on days 1 11 21 31 and 41 methotrexate IT on days 1 and 31 and pegaspargase or calaspargase pegol IV over 1-2 hours on days 2 and 22 pegaspargase or 23 calaspargase or pegaspargase IM on days 2 and 22 Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
ARMS II AND III HR B-ALL MAINTENANCE Patients receive vincristine IV on day 1 prednisolone PO BID or IV on days 1-5 mercaptopurine PO on days 1-84 methotrexate PO on days 8 15 22 29 excluded in cycles 1 and 2 36 43 50 57 64 71 and 78 and methotrexate IT on days 1 and 29 of cycles 1-2 for patients who do not receive cranial radiation Cycles repeat every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity Patients with CNS3 disease undergo cranial radiation therapy over 10 fractions during the first 4 weeks
ARM IV MPAL INDUCTION Patients receive cytarabine IT on day 1 and CNS2 patients also receive cytarabine IT on days 4 5 or 6 and 11 or 12 Patients also receive vincristine IV on days 1 8 15 and 22 daunorubicin IV over 1-15 minutes days 1 8 15 and 22 pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4 and methotrexate IT on days 8 and 29 and on days 15 and 22 for CNS3 patients Patients 10 years old receive dexamethasone PO BID or IV on days 1-14 patients 10 years old receive prednisolone PO BID or IV on days 1-28 Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
CONSOLIDATION Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29 cytarabine IV over 1-30 minutes or SC on days 1-4 8-11 29-32 and 36-39 mercaptopurine PO on days 1-14 and 29-42 methotrexate IT on days 1 8 15 and 22 excluded on days 15 and 22 for CNS3 patients vincristine IV on days 15 22 43 and 50 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on days 15 and 43 Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity Patients with testicular disease at diagnosis that does not resolve by the end of induction will and continued evidence of testicular disease at end of induction undergo testicular radiation over 12 once-daily fractions Calaspargase pegol can only be given to patients less than 22 years of age
ARM V B-LLY INDUCTION Patients receive cytarabine IT on day 1 and CNS2 patients also receive cytarabine IT on days 4 5 or 6 and 11 or 12 Patients also receive vincristine IV on days 1 8 15 and 22 daunorubicin IV over 1-15 minutes days 1 8 15 and 22 pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4 and methotrexate IT on days 8 and 29 and on days 15 and 22 for CNS3 patients Patients 10 years old receive dexamethasone PO BID or IV on days 1-14 patients 10 years old receive prednisolone PO BID or IV on days 1-28 Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
CONSOLIDATION Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29 cytarabine IV over 1-30 minutes or SC on days 1-4 8-11 29-32 and 36-39 mercaptopurine PO on days 1-14 and 29-42 methotrexate IT on days 1 8 15 and 22 excluded on days 15 and 22 CNS3 patients vincristine IV on days 15 22 43 and 50 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on days 15 and 43 Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity Patients with testicular disease at diagnosis that does not resolve by the end of induction will and continued evidence of testicular disease at end of induction undergo testicular radiation therapy over 12 once-daily fractions Calaspargase pegol can only be given to patients less than 22 years of age
ARM IV AND V MPAL AND B-LLY Post-Consolidation Therapy INTERIM MAINTENANCE I Patients receive vincristine IV on days 1 15 29 and 43 high dose methotrexate IV over 24 hours on days 1 15 29 and 43 leucovorin PO or IV on days 3-4 17-18 31-32 and 45-46 methotrexate IT on days 1 and 29 and mercaptopurine PO QD on days 1-14 15-28 29-42 and 43-56 Treatment continues for 9 weeks in the absence of disease progression or unacceptable toxicity
DELAYED INTENSIFICATION PART I Patients receive methotrexate IT on day 1 dexamethasone PO BID or IV on days 1-7 and 15-21 vincristine IV on days 1 8 and 15 doxorubicin IV over 1-15 minutes or up to 1 hour on days 1 8 and 15 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4 Treatment Parts I and II of Delayed Intensification continues for 9 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
DELAYED INTENSIFICATION PART II Patients receive cyclophosphamide IV over 30-60 minutes on day 29 thioguanine PO on days 29-42 cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39 methotrexate IT on days 29 and 36 vincristine IV or IV push over 1 minute on days 43 and 50 and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 43 Treatment Parts I and II of Delayed Intensification continues for 9 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
INTERIM MAINTENANCE II Patients receive vincristine IV on days 1 11 21 31 and 41 methotrexate IV or infusion over 2-15 minutes or 10-15 minutes on days 1 11 21 31 and 41 methotrexate IT on days 1 and 31 and pegaspargase or calaspargase pegol IV over 1-2 hours on days 2 and 22 pegaspargase or calaspargase 23 or pegaspargase IM on days 2 and 22 Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity Calaspargase pegol can only be given to patients less than 22 years of age
MAINTENANCE Patients receive vincristine IV on days 1 prednisolone PO BID or IV on days 1-5 mercaptopurine PO on days 1-84 methotrexate PO on days 8 15 22 29 excluded in cycles 1 and 2 36 43 50 57 64 71 and 78 and methotrexate IT on days 1 and 29 of cycles 1-2 for patients who do not receive cranial radiation Cycles repeat every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity Patients with CNS3 disease at diagnosis undergo cranial radiation therapy for 10 fractions over 4 weeks
Patients undergo blood sample collection and bone marrow aspiration and biopsy on study B-LLy patients undergo computed tomography CT magnetic resonance imaging MRI positron emission tomography PET andor bone scan on study
After completion of study treatment patients are followed up at 4 weeks then every 3 months for 2 years every 4-6 months for the third year then every 6-12 months for years 4-5
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2019-02845 | REGISTRY | None | None |
| AALL1732 | OTHER | None | None |
| AALL1732 | OTHER | None | None |
| U10CA180886 | NIH | CTEP | httpsreporternihgovquickSearchU10CA180886 |